Epidermal growth factor receptor 1 (EGFR) is a transmembrane protein belonging to the ErbB receptor kinase family. Overexpression of EGFR has been frequently detected in a wide range of human tumors, for examples: small cell lung cancer, small cell carcinoma of the head and neck, esophageal cancer, gastric cancer, gliomas, colon cancer, pancreas cancer, breast cancer, ovary cancer, bladder cancer, kidneys cancer, prostate cancer, etc. Cetuximab, Lapatinib, Gefitinib, and Erlotinib have shown clinical benefits to lung, colorectal, pancreatic and breast cancer patients by targeting over-expressed/activated EGFR. Furthermore, increasing evidence has demonstrated that there is a correlation between EGFR overexpression and tumor metastasis formation, therapy resistance, poor prognosis and short survival for some cancer types. It has been found that EGFR expression level is a strong prognostic indicator for head and neck, ovarian, cervical, bladder and esophageal cancer. Therefore, EGFR has become an attractive target for cancer molecular imaging and therapy.
A variety of small molecules based upon EGFR substrates and EGF have been labeled with different radionuclides for molecular imaging of EGFR expression and activity. However the small molecules and EGF based probes generally show rapid blood clearance and very low tumor uptake, thus the imaging quality is poor. Radiolabeled monoclonal antibodies (MAbs) against EGFR demonstrate good tumor uptakes, but the tumors can only be visualized at several hours or even days after injection of the probes because of both the slow tumor targeting ability and slow clearance of the radiolabeled MAbs. Thus, there is a need to find alternative imaging moieties.